DESCRIPTION: (Adapted from the application) There is evidence from a multicenter clinical trial that vitamin E slows the rate of clinical deterioration in individuals with moderately severe Alzheimer s disease (AD). The AD Cooperative Study (ADCS) is now mounting a large study to test the effects of vitamin E in persons at the earliest stage of cognitive deterioration. Older individuals with Down syndrome (DS) are at very high risk for AD. Most individuals with DS develop functional decline and show neuropathological evidence of AD by the sixth decade. The applicants propose an international multicenter randomized double-blind study to determine whether vitamin E supplementation will slow the rate of cognitive/functional decline in individuals with DS. Subjects with DS who are at least 50 years of age will be randomized into two treatment groups: vitamin E 2000 IU plus a multivitamin per day or placebo plus multivitamin. The multivitamin contains vitamin E 15 IU. The treatment period will be three years with evaluation visits every six months. The primary outcome measure will be a three year change score on a cognitive/functional measure that was derived for this purpose from the DYSPRAXIA Scale for Adults with Down Syndrome. Secondary outcome measures will include additional cognitive tests as well as informant-based measures of function and behavior.